Built on the plans of the Central State Hospital for the Insane in Indianapolis Indiana, as suggested by Dorthea Dix in 1847. The board of trustees sent M.C. Goltra to Indianapolis to obtain copies of the plans for the hospital that had just started construction there. Thus the architectural plans for the Kirkbride plan building were a copy of an asylum just begun there. The Central Indiana State Hospital for the Insane would open and accept it's patients first on November 21st 1848. The hospital and Jacksonville added several wings between 1848 and 1875.

In 1860 the hospital had 30 cases of typhoid fever with 3 deaths. This was due to a lack of a clean water supply. Dorthea Dix lobbied for funds to fix the problem and in 1862 the hospital received a 2,500,000 water reservoir and a new pumping station. The board of trustees was abolished in 1909 when executive and administrative control of all state charitable institutions passed to the newly created Board of Administration. As part of the reorganization the institution was renamed the Jacksonville State Hospital. The Civil Administrative Code of 1917 transferred jurisdiction of the hospital to the Department of Public Welfare.

For 1944-1974 the hospital participated in a departmental affiliation program for psychiatric nursing which provided instruction in psychiatric nursing to students from general hospital nursing schools. The Psychiatric Nursing Affiliation Program offered two-, three,- and four-month terms of classroom instruction and practical training at Jacksonville State Hospital.

In 1961 the Department of Mental Health assumed responsibility for Jacksonville State Hospital and in 1974 expanded the hospital's duties to include treatment for the developmentally disabled. To reflect this change in function the institution's name became the Jacksonville Mental Health and Developmental Center in 1975.

Today the facility houses developmentally ill patients. Most of the original buildings, including the Kirkbride, have been demolished. In November, 2012 the last patients were moved out and the buildings/property were declared surplus property.